1. Field of the Invention
The present invention is broadly directed to a method for enhancing anti-neoplasm effects of chemotherapies and radiation therapies with PKC inhibitors. The present invention is particularly directed to the use of Protein Kinase C (PKC) inhibitors, especially a particular class of isozyme selective PKC inhibitors in combination with an oncolytic agent or xcex3-irradiation to enhance their anti-neoplasm effects in treatment of neoplasms.
2. Description of Related Art
Therapeutic treatments have been developed over the years to treat neoplasms. There are two major approaches to treat neoplasms: 1) chemotherapy employing oncolytic agents, and 2) radiation therapy, e.g., xcex3-irradiation. Oncolytic agents and xcex3-irradiation cause cytotoxic effects, preferentially to tumor cells, and cause cell death.
Studies have shown that xcex3-irradiation and certain groups of oncolytic agents assert their cytotoxic effects by activating programmed cell death or apoptosis. A balance between the activities of apoptotic and antiapoptotic intracellular signal transduction pathways is important towards a cell""s decision of undergoing apoptosis in response to the above mentioned chemotherapy as well as radiation therapy.
PKC inhibitors has been proposed for cancer therapy, e.g. see U.S. Pat. No. 5,552,391, and PKC activities have been indicated to exert antiapoptotic effects, especially in response to radiation therapies, e.g., xcex3-irradiation. In particular, studies have shown that activation of PKC inhibits apoptosis induced by anti-neoplasm agents such as Ara-c, 2-chloro-2-deoxyadenosine, 9-xcex2-D-arabinosyl-2-fluoroadenine, and xcex3-irradiation therapy. There also have been indications that down regulation of PKC activities in tumor cells enhances apoptosis stimulated by oncolytic agents. PKC activation has been shown to attenuate xcex3-irradiation induced cell death.
There is a need in the art to develop therapeutic agents which enhance the apoptotic signal transduction pathways in cells and thereby enhance the clinical efficacy of oncolytic agents and radiation therapy.
It is an object of the invention to provide methods for treating a neoplasm.
It is another object of the invention to provide methods for enhancing an anti-neoplasm effect of an oncolytic agent.
It is still another object of the invention to provide methods for enhancing anti-neoplasm effects of radiation therapy.
These and other objects of the invention are provided by one or more of the embodiments described below.
In one embodiment of the invention there is provided a method for treating a neoplasm which comprises administrating to a mammal in need of such treatment an oncolytic agent or xcex3-irradiation in combination with a protein kinase C inhibitor.
In still another embodiment of the invention there is provided a method for enhancing an anti-neoplasm effect of chemotherapy and radiation therapy which comprises administrating a protein kinase C inhibitor in combination with said oncolytic agent or radiation therapy.
The present invention provides the art with a method for increasing apoptotic effects in cells and is thus effective in enhancing the anti-neoplasm effects of chemotherapies and radiation therapies.